Pre-erythrocytic stage malaria vaccines aim to block hepatocyte entry by sporozoites and/or release of merozoites into the blood stream, thereby circumventing the disease process and rendering the host non- infectious. The primary target of this class of vaccines is the circumsporozoite protein (CS), which is a major constituent of the sporozoite coat when it enters the host. Pre-erythrocytic immunity has been demonstrated by immunization with the CS-NANP repeat epitope, passive transfer of antibodies specific for anti-NANP repeat epitope, and immunization with irradiated sporozoites. In animal models the immunodominant CS-repeat epitope from either P.bergeii or P.yoelli, displayed on hepatitis B core particles, successfully protected >90% of animals against infection. Preliminary studies of HBc particles engineered to deliver the CS-repeat from the human parasite P.falciparum are promising, but in need of optimization. The focus of this work is to optimize the immunogenicity of the P.falciparum particle to attain the high immunogenicity and absence of genetic restriction observed with P.bergeii and P.yoelli particles. This will be achieved by optimizing the presentation of the NANP repeat epitope at the surface of HBc and incorporating a universal malaria- specific T cell epitope. Once identified, this vaccine candidate will be the subject of clinical testing during phase II. PROPOSED COMMERCIAL APPLICATION: Malaria is by far the world's most important tropical parasitic disease, and kills more people than any other communicable disease, with the exception of tuberculosis. Malaria is a public health problem in more than 90 countries, inhabited by a total of 2.4 billion people - 40% of the world's population. Mortality due to malaria is estimated to be in the range of 1.5 to 2.7 million deaths each year, according for one person every 12 seconds. There are 7 million travelers from the U.S. each year to endemic areas.